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ToxSci Advance Access originally published online on August 13, 2007
Toxicological Sciences 2007 100(1):215-223; doi:10.1093/toxsci/kfm202
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

High Dietary Inorganic Phosphate Affects Lung through Altering Protein Translation, Cell Cycle, and Angiogenesis in Developing Mice

Hua Jin*,1, Seung-Hee Chang*,1, Cheng-Xiong Xu*, Ji-Young Shin*, Youn-Sun Chung*, Sung-Jin Park*, Yeon-Sook Lee{dagger}, Gil-Hwan An{ddagger}, Kee-Ho Lee§ and Myung-Haing Cho*,¶,2

* Laboratory of Toxicology, College of Veterinary Medicine {dagger} Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 151-742, Korea {ddagger} Department of Food Science & Technology, Chungnam National University, Taejeon 305-764, Korea § Laboratory of Radiation Molecular Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea 139-706 Nano Systems Institute-National Core Research Center, Seoul National University, Seoul 151-742, Korea

2 To whom correspondence should be addressed. Fax: (82) 2-873-1268. E-mail: mchotox{at}snu.ac.kr.

Received April 30, 2007; accepted August 2, 2007


  Abstract

Inorganic phosphate (Pi) plays a key role in diverse physiological functions. Several studies indicate that Pi may affect lung cell development through Na/Pi cotransporter (NPT). Several NPT subtypes have been identified in mammalian lung, and considerable progress has been made in our understanding of their function and regulation. Therefore, current study was performed to elucidate the potential effects of high dietary Pi on lungs of developing mice. Our results clearly demonstrate that high dietary Pi may affect the lung of developing mice through Akt-related cap-dependent protein translation, cell cycle regulation, and angiogenesis. Our results support the hypothesis that Pi works as a critical signal molecule for normal lung growth and suggest that careful restriction of Pi consumption may be important in maintaining a normal development.

Key Words: Akt; protein translation; cell cycle; angiogenesis; lung; inorganic phosphate.

1 These authors contributed equally to this work.


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